Abstract
BACKGROUND: Gut microbiome is critical to our human health and is related to postmenopausal osteoporosis (PMO). Strontium ranelate (SrR) is an anti-osteoporosis oral drug that can promote osteoblast formation and inhibit osteoclast formation. However, the effect of SrR on gut microbiome has been rarely studied. Therefore, we investigated the effect of oral SrR on gut microbiome and metabolic profiles. RESULTS: In this study, we used ovariectomized (OVX) Sprague-Dawley rats to construct a PMO model and applied oral SrR for 6 weeks. The relative abundance of intestinal microbiome was investigated by 16S rRNA metagenomic sequencing. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to analyze changes in metabolites of intestinal contents. Results demonstrated that 6-week oral SrR alleviated osteoporosis and significantly changed the composition of the gut microbiome and metabolic profiles of OVX rats. Ruminococcus, Akkermansia and Oscillospira were significantly enriched in the gut of OVX rats after 6-week oral SrR. Especially, the species R. albus showed the greatest importance by a random forest classifier between OVX and OVX_Sr group. The enrichment of R. albus in the gut was positively correlated with bone mineral density and the accumulation of lycopene and glutaric acid, which also significantly elevated after oral SrR. CONCLUSIONS: We discovered that oral SrR can improve bone health while stimulate the accumulation of gut microbe R. albus and metabolites (lycopene and glutaric acid). The results suggested possible connections between oral SrR and the gut-bone axis, which may provide new insight into the treatment/prevention of osteoporosis.